2.1 Breast Cancer
Breast cancer is the most common cancer among women. Every year, more than 1,500,000 women in the world are diagnosed with breast cancer and 700,000 die because of breast cancer. As the most deadly cancer in women under age 55 (lung cancer is the leader beyond that age), breast cancer strikes one out of every 8 American women. Caucasians are 4 times more likely to get breast cancer than Hispanics, Blacks or Asians. The breast cancer incidence rate increased by about 4% per year during the 1980s though death rates from breast cancer declined significantly during 1992 to 1996, with the largest decreases in younger women.
The most common feature of breast cancer is a breast lump. The lump may or may not be painful. Sometimes the nipple may be increasingly puckered or there is swelling of the skin of the breast. There may be a discharge from the nipple. Oftentimes, the lymph glands of the armpit may also be enlarged. Less common symptoms include nipple erosion or ulceration, diffuse erythema of the breast, and axillary adenopathy. A suspicious breast lump is usually subjected to an x-ray examination called a mammogram and a needle biopsy. Breast cancer has a very high cure rate, with 97% of women surviving for 5 years if the cancer is diagnosed early.
The exact cause to most breast cancer are unknown. However, numerous risk factors have been identified. Simply being a woman is the main risk factor for developing breast cancer. Breast cancer can affect men, but this disease is about 100 times more common among women than men. A woman's risk of developing breast cancer increases with age. About 77% of women with breast cancer are over age 50 at the time of diagnosis while women younger than 30 years account for only 0.3% of breast cancer cases. Recent studies have shown that about 10% of breast cancer cases are directly due inherited mutations in the BRCA1 and BRCA2 genes and the p53 tumor suppressor gene. Breast cancer risk is higher among women whose close blood relatives have this disease. A woman with cancer in one breast has a 3 to 4-fold increased risk of developing a new cancer in the other breast or in another part of the same breast, which is different from a recurrence of the first cancer. Other risk factors include chest area radiation therapy, early menstruation or late menopause, the use of oral contraceptives, no children or having a first child after age 30, long-term use of hormone replacement therapy after menopause, no breast feeding, use of alcohol, obesity and high-fat diets, physical inactivity, exposure to environmental pollutants (e.g., pesticides like DDE (chemically related to DDT) and PCBs (polychlorinated biphenyls).
The staging of breast cancer is based on the revised criteria of TNM staging by the American Joint Committee for Cancer (AJCC) published in 1988. Staging is the process of describing the extent to which cancer has spread from the site of its origin. It is used to assess a patient's prognosis and to determine the choice of therapy. The stage of a cancer is determined by the size and location in the body of the primary tumor, and whether it has spread to other areas of the body. Staging involves using the letters T, N and M to assess tumors by the size of the primary tumor (T); the degree to which regional lymph nodes (N) are involved; and the absence or presence of distant metastases (M)—cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes. Each of these categories is further classified with a number 1 through 4 to give the total stage. Once the T, N and M are determined, a “stage” of I, II, III or IV is assigned. Stage I cancers are small, localized and usually curable. Stage II and III cancers typically are locally advanced and/or have spread to local lymph nodes. Stage IV cancers usually are metastatic (have spread to distant parts of the body) and generally are considered inoperable.
There are several types of breast cancer. Adenocarcinoma (ductal carcinomas and lobular carcinomas) is a general type of cancer that starts in glandular tissues of the breast. Ductal carcinoma in situ (DCIS), also known as intraductal carcinoma, is the most common type of noninvasive breast cancer. Comedocarcinoma is often used to describe a type of DCIS with necrosis. Infiltrating (or invasive) ductal carcinoma (IDC), accounting for about 80% of invasive breast cancers, usually starts in a milk passage, or duct, of the breast, and invades the fatty tissue of the breast with the potential to metastasize, or spread, to other parts of the body through the lymphatic system and bloodstream. Infiltrating (or invasive) lobular carcinoma (ILC) starts in the milk-producing glands and accounts for about 10% to 15% of invasive breast cancers. A rare type of invasive breast cancer is inflammatory breast cancer, which accounts for only about 1% of all breast cancers. Other breast cancer types include in situ, lobular carcinoma in situ (LCIS), medullary carcinoma (5%), mucinous carcinoma, phyllodes tumor, tubular carcinoma (2%), and Paget's disease of the nipple.
Breast cancer can be treated with surgery, radiation therapy, chemotherapy, surveillance, adjuvant (additional), or a combination of these treatments. There are many different types of surgery for breast cancer. Options include removing the whole breast and certain other tissues (radical, modified radical, and total mastectomy) or removing only the lump with or without some tissue around it (lumpectomy and partial mastectomy). Unfortunately, these procedures often lead to pain, as well as reduced use of the arm and shoulder. Further, women who have a large lump removed from a small breast are likely to notice a significant change in the shape of the breast. Although those who have a breast removed may choose to have it rebuilt using their own tissue or a silicone or saline implant, sometimes, leaks may cause other cancers and certain immune system disorders.
Radiation is always given after breast conservation surgery (lumpectomy or a partial/segmental mastectomy). It may also be given after a full mastectomy, especially to women with large tumors or those with evidence of tumor cells at the edge of the tissue that is removed. Radiation is used in both early and advanced stage cancer, as well as in cancer that recurs in the chest wall after mastectomy. Radiation is also used to shrink an especially large tumor prior to surgery or to slow the growth of inoperable tumors using either external beam (similar to an x-ray) or brachytherapy (internal radiation delivered with implanted radioactive seeds). Fatigue is a possible side effect of radiation therapy, but it gradually ceases after treatment is completed.
Because some breast cancers seem to be nourished by the female hormone estrogen (or sometimes progesterone), doctors often prescribe therapy that blocks or eliminates a woman's natural supply of these hormones. In some relatively rare cases, the ovaries (which make the female hormones) are removed surgically. Although Tamoxifen®, the most widely used hormone blocker, has proved to be very effective in suppressing recurrence of cancer in the same breast and prevent breast cancer in the other breast, it may increase risk of endometrial cancer, and can cause bone loss among premenopausal women. Tamoxifen® has also been linked to blood clots in the major veins and the lungs. Other alternatives include Zoladex® (goserelin acetate) and Faslodex® (fulvestrant)
Chemotherapy is used primarily in cases where the disease has spread outside the breast and where hormonal treatments alone are no longer effective in preventing tumor growth. Potential side effects include nausea and vomiting, loss of hair, low blood cell counts, and fatigue. Many chemotherapeutic drugs have been tried in the past as single agents for the palliation of breast cancer, but the results were generally disappointing. Nevertheless, the role of chemotherapy in the management of breast cancer is continually evolving. Oftentimes, chemotherapy with radiation in adjunct to surgery is used. In general, chemotherapy can achieve long-term survival rates of up to 15% to 20%, even in patients with recurrent or metastatic disease (Ali et al., 2000, Oncology 14(8):1223–30). Unfortunately, the high initial response rates to first line chemotherapy does not appear to translate into a survival benefit (Kohno and Kitahara, 2001, Gan To Kagaku Ryoho 28(4):448–53). Moreover, there are many undesirable side effects associated with chemotherapy such as temporary hair loss, mouth sores, anemia (decreased numbers of red blood cells that may cause fatigue, dizziness, and shortness of breath), leukopenia (decreased numbers of white blood cells that may lower resistance to infection), thrombocytopenia (decreased numbers of platelets that may lead to easy bleeding or bruising), and gastrointestinal symptoms like nausea, vomiting, and diarrhea. Active chemotherapeutic agents include Taxol® (paclitaxel), epirubicin, Taxotere®, Tamoxifen® (Nolvadex), Evista® (raloxifene), Fareston (toremifene), Aromasin® (exemestane), Femara® (letrozole), Arimidex® (anastrozole), Megace® (megestrol), and Herceptin® (trastuzumab).
The identification of active chemotherapeutic agents against cancers traditionally involved the use of various animal models of cancer. The mouse has been one of the most informative and productive experimental system for studying carcinogenesis (Sills et al., 2001, Toxicol Letters 120:187–198), cancer therapy (Malkinson, 2001, Lung Cancer 32(3):265–279; Hoffman R M., 1999, Invest New Drugs 17(4):343–359), and cancer chemoprevention (Yun, 1999, Annals NY Acad Sci. 889:157–192). Cancer research started with transplanted tumors in animals which provided reproducible and controllable materials for investigation. Pieces of primary animal tumors, cell suspensions made from these tumors, and immortal cell lines established from these tumor cells propagate when transplanted to animals of the same species.
To transplant human cancer to an animal and to prevent its destruction by rejection, the immune system of the animal are compromised. While originally accomplished by irradiation, thymectomy, and application of steroids to eliminate acquired immunity, nude mice that are athymic congenitally have been used as recipients of a variety of human tumors (Rygaard, 1983, in 13th International Cancer Congress Part C, Biology of Cancer (2), pp 37–44, Alan R. Liss, Inc., NY; Fergusson and Smith, 1987, Thorax, 42:753–758). While the athymic nude mouse model provides useful models to study a large number of human tumors in vivo, it does not develop spontaneous metastases and are not suitable for all types of tumors. Next, the severe combined immunodeficient (SCID) mice is developed in which the acquired immune system is completely disabled by a genetic mutation. Human lung cancer was first used to demonstrate the successful engraftment of a human cancer in the SCID mouse model (Reddy S., 1987, Cancer Res. 47(9):2456–2460). Subsequently, the SCID mouse model have been shown to allow disseminated metastatic growths for a number of human tumors, particularly hematologic disorders and malignant melanoma (Mueller and Reisfeld, 1991, Cancer Metastasis Rev. 10(3):193–200; Bankert et al., 2001, Trends Immunol. 22:386–393). With the recent advent of transgenic technology, the mouse genome has become the primary mammalian genetic model for the study of cancer (Resor et al., 2001, Human Molec Genet. 10:669–675).
While surgery, chemotherapeutic agents and radiation are useful in the treatment of breast cancer, there is a continued need to find better treatment modalities and approaches to manage the disease that are more effective and less toxic, especially when clinical oncologists are giving increased attention to the quality of life of cancer patients. The present invention provides an alternative approach to cancer therapy and management of the disease by using an oral composition comprising yeasts.
2.2 Yeast-Based Compositions
Yeasts and components thereof have been developed to be used as dietary supplement or pharmaceuticals. However, none of the prior methods uses yeast cells which have been cultured in an electromagnetic field to produce a product that has an anti-cancer effect. The following are some examples of prior uses of yeast cells and components thereof:
U.S. Pat. No. 6,197,295 discloses a selenium-enriched dried yeast product which can be used as dietary supplement. The yeast strain Saccharomyces boulardii sequela PY 31 (ATCC 74366) is cultured in the presence of selenium salts and contains 300 to about 6,000 ppm intracellular selenium. Methods for reducing tumor cell growth by administration of the selenium yeast product in combination with chemotherapeutic agents is also disclosed.
U.S. Pat. No. 6,143,731 discloses a dietary additive containing whole β-glucans derived from yeast, which when administered to animals and humans, provide a source of fiber in the diet, a fecal bulking agent, a source of short chain fatty acids, reduce cholesterol and LDL, and raises HDL levels.
U.S. Pat. No. 5,504,079 discloses a method of stimulating an immune response in a subject utilizing modified yeast glucans which have enhanced immunobiologic activity. The modified glucans are prepared from the cell wall of Saccharomyces yeasts, and can be administered in a variety of routes including, for example, the oral, intravenous, subcutaneous, topical, and intranasal route.
U.S. Pat. No. 4,348,483 discloses a process for preparing a chromium yeast product which has a high intracellular chromium content. The process comprises allowing the yeast cells to absorb chromium under a controlled acidic pH and, thereafter inducing the yeast cells to grow by adding nutrients. The yeast cells are dried and used as a dietary supplement.
Citation of documents herein is not intended as an admission that any of the documents cited herein is pertinent prior art, or an admission that the cited documents are considered material to the patentability of the claims of the present application. All statements as to the date or representations as to the contents of these documents are based on the information available to the applicant and does not constitute any admission as to the correctness of the dates or contents of these documents.